Generation of a canine anti-canine CD20 antibody for canine lymphoma treatment

Abstract Lymphoma is the most common hematological cancer in dogs. Canine diffuse large B cell lymphoma shows a relatively good response to treatment with multi-agent cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy; however, the 2-year survival rate is as low as 20%. F...

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Autores principales:	Takuya Mizuno, Yukinari Kato, Mika K. Kaneko, Yusuke Sakai, Toshinori Shiga, Masahiro Kato, Toshihiro Tsukui, Hirofumi Takemoto, Akio Tokimasa, Kenji Baba, Yuki Nemoto, Osamu Sakai, Masaya Igase
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e1433744f59a4ad9a18dbad654843c03
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spelling	oai:doaj.org-article:e1433744f59a4ad9a18dbad654843c032021-12-02T15:39:40ZGeneration of a canine anti-canine CD20 antibody for canine lymphoma treatment10.1038/s41598-020-68470-92045-2322https://doaj.org/article/e1433744f59a4ad9a18dbad654843c032020-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-68470-9https://doaj.org/toc/2045-2322Abstract Lymphoma is the most common hematological cancer in dogs. Canine diffuse large B cell lymphoma shows a relatively good response to treatment with multi-agent cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy; however, the 2-year survival rate is as low as 20%. For human B cell type lymphoma, the anti-CD20 chimeric antibody, rituximab, was developed two decades ago. The combination of rituximab and CHOP chemotherapy was highly successful in improving patient prognosis. However, no anti-canine CD20 antibody is available for the treatment of canine lymphoma. During this study, a rat anti-canine CD20 monoclonal antibody was established. We also generated a rat-canine chimeric antibody against canine CD20 designed for clinical application. This chimeric antibody (4E1-7-B) showed in vitro antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against the canine B cell lymphoma cell line CLBL-1. Moreover, to obtain stronger ADCC activity, a defucosylated 4E1-7-B antibody (4E1-7-B_f) was also generated, and it showed tenfold stronger ADCC activity compared with 4E1-7-B. 4E1-7-B_f as well as 4E1-7-B suppressed the growth of CLBL-1 tumors in an immunodeficient xenotransplant mouse model. Finally, a single administration of 4E1-7-B_f induced considerable peripheral B cell depletion in healthy beagles. Thus, 4E1-7-B_f is a good antibody drug candidate for canine B cell type lymphoma.Takuya MizunoYukinari KatoMika K. KanekoYusuke SakaiToshinori ShigaMasahiro KatoToshihiro TsukuiHirofumi TakemotoAkio TokimasaKenji BabaYuki NemotoOsamu SakaiMasaya IgaseNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takuya Mizuno Yukinari Kato Mika K. Kaneko Yusuke Sakai Toshinori Shiga Masahiro Kato Toshihiro Tsukui Hirofumi Takemoto Akio Tokimasa Kenji Baba Yuki Nemoto Osamu Sakai Masaya Igase Generation of a canine anti-canine CD20 antibody for canine lymphoma treatment
description	Abstract Lymphoma is the most common hematological cancer in dogs. Canine diffuse large B cell lymphoma shows a relatively good response to treatment with multi-agent cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy; however, the 2-year survival rate is as low as 20%. For human B cell type lymphoma, the anti-CD20 chimeric antibody, rituximab, was developed two decades ago. The combination of rituximab and CHOP chemotherapy was highly successful in improving patient prognosis. However, no anti-canine CD20 antibody is available for the treatment of canine lymphoma. During this study, a rat anti-canine CD20 monoclonal antibody was established. We also generated a rat-canine chimeric antibody against canine CD20 designed for clinical application. This chimeric antibody (4E1-7-B) showed in vitro antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against the canine B cell lymphoma cell line CLBL-1. Moreover, to obtain stronger ADCC activity, a defucosylated 4E1-7-B antibody (4E1-7-B_f) was also generated, and it showed tenfold stronger ADCC activity compared with 4E1-7-B. 4E1-7-B_f as well as 4E1-7-B suppressed the growth of CLBL-1 tumors in an immunodeficient xenotransplant mouse model. Finally, a single administration of 4E1-7-B_f induced considerable peripheral B cell depletion in healthy beagles. Thus, 4E1-7-B_f is a good antibody drug candidate for canine B cell type lymphoma.
format	article
author	Takuya Mizuno Yukinari Kato Mika K. Kaneko Yusuke Sakai Toshinori Shiga Masahiro Kato Toshihiro Tsukui Hirofumi Takemoto Akio Tokimasa Kenji Baba Yuki Nemoto Osamu Sakai Masaya Igase
author_facet	Takuya Mizuno Yukinari Kato Mika K. Kaneko Yusuke Sakai Toshinori Shiga Masahiro Kato Toshihiro Tsukui Hirofumi Takemoto Akio Tokimasa Kenji Baba Yuki Nemoto Osamu Sakai Masaya Igase
author_sort	Takuya Mizuno
title	Generation of a canine anti-canine CD20 antibody for canine lymphoma treatment
title_short	Generation of a canine anti-canine CD20 antibody for canine lymphoma treatment
title_full	Generation of a canine anti-canine CD20 antibody for canine lymphoma treatment
title_fullStr	Generation of a canine anti-canine CD20 antibody for canine lymphoma treatment
title_full_unstemmed	Generation of a canine anti-canine CD20 antibody for canine lymphoma treatment
title_sort	generation of a canine anti-canine cd20 antibody for canine lymphoma treatment
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/e1433744f59a4ad9a18dbad654843c03
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Generation of a canine anti-canine CD20 antibody for canine lymphoma treatment

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